Light entrainment of the mammalian circadian clock requires input from the retina, which communicates with the suprachiasmatic nucleus (SCN) via the retinohypo-thalamic tract (RHT). This connection is formed by the axonal projections of a small subset of retinal ganglion cells (RGCs). Surprisingly, rod and cone photoreceptors are not required; instead, RGCs that project to the SCN seem to function as autonomous circadian photoreceptors, and exhibit light responses independent of rod- and cone-driven synaptic input. These SCN-projecting RGCs also express melanopsin, a novel opsin-like protein, which has been proposed to be the elusive photopigment of the circadian system. The overall goal of this research is to characterize the biochemical and spectral properties of melanopsin to determine if it mediates the intrinsic light responses of SCN-projecting RGCs. [unreadable] [unreadable]